Nerve inflammatory disease mainly refers to the course triggered by neurospongium abnormality (microglial cell and astrocyte cell) or chronical activation. This kind of neurospongium with over-activating status causes high level falmmory and oxidative stress response molecules, resulting in injury or death of nerve cells. Injury or death of nerve cells may also induce activation of neurospongium, and boost locally harmful cycle propagation of nerve inflammation. Prior art has proven that nerve inflammatory response can be effectively restrained by suppression of neurospongium, especially microglia. Nerve inflammatory disease includes Senile Dementia (Alzheimer's disease), Parkinson's disease, Amyotrophic lateral sclerosis, autoimmune disease, Prion disease apoplexy, traumatic brain injury, spinal muscular atrophy, disseminated sclerosis, epilepsia, neuropathic pain, etc.
Senile Dementia is also named Alzheimer's disease (AD), the morbidity of which is No. 1 among all kinds of neurodegenerative diseases; AD is a central nervous system degenerative disease mainly causes progressive cognitive impairment and memory ability damage. The clinical manifestation of the disease is dysfunction of recent memory, following by persistent intelligence impairment, judgment and reasoning ability lose, aphasia, and dyskinesia etc. The pathological characteristics are a lot of senile plaques (SPs) and neurofibrilary tangles (NFTs).
Piperazine compounds have the function of selective inhibition of glial activation pathway (referring to WO03/018563). Chinese patent CN101754762 discloses piperazine compounds for treating nerve inflammatory diseases. Wenhui Hu et al. discloses minozac and a compound represented by formula (II) (referring to Bioorganic & Medicinal Chemistry Letters 17 (2007)414-418) having the activity against Senile Dementia.
